环腺苷一磷酸对人Ⅰ型17β羟类固醇脱氢酶在绒癌细胞系中表达的调节作用

REGULATION OF HUMAN 17β-HYDROXYSTEROID DEHYDROGENASE TYPE 1 EXPRESSION BY CYCLIC ADENOSINE 3', 5'-MONOPHOSPHATE IN CHORIOCARCINOMA CELLS

由HSD17B1基因编码的人Ⅰ型17β-羟类固醇脱氢酶(17β-hydroxysteroid dehydrogenasetype 1,简称Ⅰ型17HSD)催化雌酮与雌二醇之间的转化。本文研究环腺苷一磷酸简称(cAM-P)对该酶在培养的绒癌细胞系(JAR和JEG-3)中表达的调节作用。用8-bromo-cAMP处理两种绒癌细胞后,观察到在伴随1.3 kbⅠ型17 HSDmRNA表达的同时,Ⅰ型17 HSD蛋白浓度也显著上升。标记基因分析表明,cAMP可诱导HSD 17 B1基因启动子在JAR和JEG-3细胞系中的转录活性,参与调节这一诱导作用的区域位于HSD 17 B1基因编码区上游-659至-550处。凝胶阻滞实验显示这一区域可同JAR、JEG-3、T-47 D和HeLa细胞核抽提物形成特异的DNA-蛋白复合物。本结果首次证实cAMP激活HSD 17 B1基因启动子在绒癌细胞中的转录。

Human 17 p-hydroxysteroid dehydro-genase type 1 (17 HSD type 1), encoded by HSD 17 B 1 gene, is a steroidogenic enzyme catalyzing the interconversion of estrone and estradiol. In this study, we investigated the role of cyclic adenosine 3', 5'-monophosphate (cAMP) in the regulation of 17 HSD type 1 expression in cultured choriocarcinoma cell lines. Treatment with 8-bromo-cAMP increased 17-HSD type 1 protein concentration in JAR and JEG-3 cells, and the induction was accompanied by parallel increase of 1.3 kb 17 HSD type 1 mRNA expression. Reporter gene analysis revealed that the activity of HSD 17 B 1 promoter in JAR and JEG-3 cells was induced by cAMP and that the region participating in transmission of cAMP effect is situated in the position between -659 and -550 in HSD 17 B 1 gene. The consequent elec-trophoretic mobility shift assay showed that this region formed specific DNA-protein complexes with nuclear extracts prepared from JAR, JEG-3, T-47 D and HeLa cells. The data provide the first evidence that HSD 17 B 1 gene transcription is activated by cAMP in choriocarcinoma cells.